We usually discuss advanced glycation endproducts (AGEs) in the context of slow, lifelong accumulation of nonenzymatic reaction between protein and sugars. Until recently, I hadn’t realized that the diet is also a major source of AGE and AGE-related damage. I learned about the extrinsic source of AGEs from a recent study that showed diets lower in AGE (i.e., products of the Maillard reaction — outside the body, usually the heat-catalyzed reaction of hexose and pentoses with muscle proteins in cooked meat) alleviate both cardiac and kidney fibrosis.
On a related note, it turns out that most renoprotective measures taken to prevent damage to diabetic kidneys have something in common — surprisingly, it’s not that they lower blood sugar, rather but that they retard or prevent the formation of AGEs in the kidney, suggesting a causative role for AGEs at least in diabetes-related nephropathy.
How might AGEs cause age-related damage in the kidney and other tissues? One mechanism might involve AGE-induced production of matrix metallproteases (MMPs) by fibroblasts. MMPs are known to break down the extracellular matrix, weakening the structural integrity of a tissue and also promoting metastatic invasion by cancer cells.
Ouroboros 